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Retatrutide

78
evidence score
fat loss
Research Only
122 studies
LY3437943triple agonistGLP-1 GIP glucagon agonist

Retatrutide is an investigational triple agonist of GLP-1, GIP, and glucagon receptors developed by Eli Lilly. Phase II data demonstrated 24.2% average weight loss at 24 weeks — exceeding any approved therapy. Glucagon agonism adds hepatic fat mobilization and energy expenditure beyond dual GLP-1/GIP. Currently in Phase III trials for obesity and type 2 diabetes. Not available outside clinical trials; compounded versions circulate in gray market. Represents the next frontier of obesity pharmacology.

Evidence

Strong evidence

Safety

Unknown safety profile

Clinical Status

Phase III

Last Sync

Feb 19, 2026

Last Reviewed

Not reviewed yet

Physician Notes

The glucagon component may cause transient heart rate increase. Start at lowest dose. Dysesthesia reported in some patients.

FDA Status:Phase 3 clinical trials. Available via compounding in some jurisdictions.

Monitoring

  • HbA1c/fasting glucose q3mo
  • Heart rate monitoring
  • Liver function (glucagon component)
  • Weight + body composition q3mo

Contraindications

  • Same as tirzepatide/semaglutide class
  • Hepatic insufficiency (relative)
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Dosing

Typical
8 mg
1 mgRange12 mg
FrequencyOnce weekly subcutaneous (trial doses)

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Pharmacology

Half-life~6 days (estimated)
OnsetWeeks for weight loss; appetite suppression within days
DurationOngoing; effects reverse after discontinuation
Routes
subcutaneous

Evidence Score

78
Level A — Strong
122 studies indexed · 8 meta-analyses
Scoring Factors
Volume(24%)~42/100
Quality(24%)~55/100
Sample Size(12%)~100/100
Consistency(14%)~100/100
Replication(8%)~100/100
Recency(18%)~100/100

Scores estimated from study counts. Exact breakdown computed after research sync.

Evidence Levels
AScore ≥75 with at least 1 meta-analysis and 3+ RCTs
BScore ≥50 with at least 1 RCT or meta-analysis
CScore ≥25 — observational or animal evidence only
DScore <25 — very limited or preclinical data

Plain-English Snapshot

Retatrutide is currently categorized as a fat loss compound.

Evidence is strong (78/100) with a relatively mature body of research (122 indexed studies).

Safety scoring is incomplete. Start conservatively and monitor carefully.

Core mechanism

Triple GLP-1/GIP/glucagon receptor agonist; adds hepatic fat mobilization and increased energy expenditure to GLP-1/GIP incretin effects

Practical Context

Strongest current signals

  • Level A: Incretin Dominance and Emerging Mechanisms in Obesity Pharmacotherapy: Insights from 275 Registered Clinical Trials (2019-2024).
  • Level A: Effect of GLP-1 receptor agonists and co-agonists on atrial fibrillation risk in overweight or obesity: systematic review and meta-analysis of randomized controlled trials.
  • Level A: Comparative Meta-Analysis of Retatrutide Versus Placebo and Dulaglutide for Weight Loss and Diabetes Management: Insights From Clinical Trials.

Elevated caution signals

1 severe/high side effect flag

Compound Profile